The immunopathologic effect of infection with rabies serogroup viruses will be studied in cell culture and mice. Tissue culture models will be used to characterize by avidity, specificity, and molecular class the antibody type which is lytic to infected cells. Non-lytic and lytic antibody will then be evaluated in infected mice for protective capacity or ability to mediate an immunopathologic reaction. Immune mouse lymphoid cell populations or subpopulations will also be tested in tissue culture and mice for effect on the course of rabies virus infection. The immune responses of mice infected with rabies serogroup viruses will be evaluated by in vitro methods for the quantitative and qualitative measurement of both antibody and cell-mediated immune response. Lymphocyte responsiveness will be related to clinical signs, brain lesions, and virus titers in donar mice. These tests will explore two hypotheses which might explain the early death phenomenon in vaccinated animals and prolonged life in immunosuppressed mice: 1) antibody (or an as yet unidentified class of antibody) kills rabies virusinfected cells directly; 2) antibody or soluble antigen prevents the protective effect of cell-mediated immunity and thus promotes killing of cells by virus.